As previously reported, the cytotoxicity of bleomycin (BLM) toward cultured mammalian cells was remarkably potentiated by vortex-stirring this agent with the cells for a few seconds in the presence of high molecular weight polyacrylic acid (PAA). This paper describes that the enhancement of BLM cytotoxicity was also achieved by a sequential BLM-treatment immediately after vortex-stirring cells with PAA only. It was suggested that this enhancement resulted from the transient permeabilization of the plasma membrane induced during vortex-stirring in the presence of PAA, leading to an increase in BLM incorporation. This mechanism was supported by the finding of an appreciable uptake by vortex-stirred cells of Lucifer Yellow, a known non-permeant material. This procedure, which did not affect any cell viability, might be a beneficial method for transient permeabilization of cultured mammalian cells to facilitate the internalization of non-permeant materials.